Electrophysiological studies on EMD 23 448, an indolyl-3-butylamine, in the rat: a putative selective dopamine autoreceptor agonist

Single unit electrophysiological and microiontophoretic techniques were used to study the effects of a putative selective dopamine autoreceptor agonist, EMD 23 448, an indolyl-3-butylamine on the activity of both dopamine neurons in the substantia nigra and dopamine-sensitive neurons in the caudate nucleus. Intravenous administration of EMD 23 448 inhibited the firing of dopamine neurons in the nigra in a dose-dependent manner. This effect could be readily reversed by the subsequent intravenous administration of the dopamine receptor antagonist, haloperidol. Microiontophoretic application of EMD 23 448 onto these neurons also inhibited their activity and this effect was blocked by iontophoresis of the dopamine receptor antagonist, trifluoperazine. Intravenous administration of the former compound increased the activity of dopamine-sensitive cells in the caudate in the same doses which inhibited dopamine neurons in the nigra. However, this effect appeared to be indirect since the iontophoretic application of EMD 23 448 directly onto caudate neurons had no effect on their firing rate. In addition, the activity of norepinephrine-containing neurons in the locus coruleus and serotonin-containing cells in the dorsal raphé nucleus was not changed by direct microiontophoretic application of this compound. In contrast, EMD 23 448 selectively blocked the acetylcholine-induced activation of pyramidal neurons in the hippocampus. These findings provide further evidence that with respect to central catecholamine neurons EMD 23 448 may be a selective agonist for dopamine autoreceptors.